The Clinical and Specimen Core comprises two units: the Participant Accrual and Retention (PAR) Unit and the Specimen Collection, Processing, and Management (SCPM) Unit. These units work closely to identify transmission pairs and to collect clinical samples to address the specific aims of Projects 1 and 2. The San Diego First Choice Programthe foundation of the PAR Unithas assembled the single largest cohort of participants with primary HIV infection and the single largest cohort of phylogenetically linked transmitting pairs. Large numbers of both types of study participants are needed to provide critical insights into the determinants of HIV transmission, together with a systematic, prospective analysis of factors that may impact transmission. The Clinical and Specimen Core will identify, recruit, and enroll study subjects and collect, process, store and manage clinical specimens needed to meet the program objectives. The PAR Unit will (1) identify and recruit individuals with acute (HIV EIA negative) and very early (detuned EIA O.D. < 0.3) HIV infection (index+ participants); (2) identify and recruit exposed but HIVindividuals (index- participants); (3) collect and manage behavioral and clinical data from follow-up of index+ participants who remain antiretroviral-treatment naive (graduated index+ participants); and (4) identify and recruit sexual partners of these index participants. Based on our previous success in the First Choice Program, we will continue to identify and recruit index participants through community referral. Modeled after successful CDC programs, we will implement respondent driven sampling (RDS) using select acutely infected index participants as seeds. We will also implement nucleic acid testing (NAT) and detuned EIA testing in multiple San Diego County HIV testing sites. With these strategies, we expect to enroll at least 85 index+ participants annually. To identify and recruit the sexual partners of the index participants, we will use standard contact tracing and more novel e-mail notification and molecular epidemiologic approaches. Through these methods, we expect to recruit 23 epidemiologically and phylogenetically linked transmission pairs, 35 epidemiologically unlinked but phylogenetically linked transmission pairs, and 24 epidemiologically linked serodiscordant nontransmitting pairs annually. The SCPM Unit will (1) collect and process all clinical specimens; (2) inventory, store, track, and ship all specimens locally and to collaborating sites; (3) obtain consent and enroll recipients of confidential HIV counseling and testing in San Diego County to detect acute infection via NAT and early infection via detuned EIA; and (4) process > 11,000 blood samples for NAT and > 170 blood samples for LS EIA testing annually.